A number of diverse drugs have been found effective against malaria. However in many cases, the initial success of physicians in treating this disease is followed by total failure. Drugs which worked initially become totally ineffective after a period of time. An initial period of remission is often followed by a period of frustration during which nothing seems to be effective against the disease. Death becomes inevitable.
Such a phenomenon is often referred to as multidrug resistance. A material cell which initially responds to treatment by one or more drugs becomes resistant to treatment by not only the drug previously used, but but any malarial treatment drug. Martin, Odula and Milhous disclosed the treatment of such multidrug resistance in malaria by using verapamil. "Reversal of Chloroquine Resistance in Plasmodium falciparaum by Verapamil," Martin et al, Science, Feb. 28, 1987. Martin et al, reports that Verapamil did reverse chloroquine resistance in malaria cells, but that the verapamil alone had no effect on the malaria.
The structural formula of verapamil is shown below: ##STR1##
The problem with this approach is that verapamil is a calcium channel blocker. While calcium channel blockers are therapeutic in the treatment of hypertension at moderate levels, they are toxic at levels high enough to effect MDR reversal.
Consequently, researchers throughout the world continue to press for techniques for reversing multidrug resistance. A successful clinical technique for reversing multidrug resistance in malaria will be one of the most important breakthroughs in the fight against malaria.